Block 6: Functional Groups II Flashcards
How does ethanol act as a base?
CH3CH2OH + Na+NH2- –> CH3CH2O-Na+ + NH3
How does ethanol act as an acid?
CH3CH2OH + H2SO4 —> CH3CH2OH2 + HSO4-
What is the conjugate base of an alcohol called?
An alkoxide ion
What is the conjugate acid of an alcohol called?
An oxonium ion
Why are the alkoxide and oxonium ions important?
They act as EXCELLENT nucleophiles and electrophiles in the synthesis of organic compounds
Are phenols acidic or basic?
Phenols are vaguely acidic as their conjugate base in an electron donating group, causing the ring to become resonance stabilized.
How do electron withdrawing groups affect the acidity of a phenol?
They make it more acidic as they stabilize the phenoxide anion further
How do electron donating groups affect the acidity of a phenol?
They make it less acidic as they destabilze the phenoxide anion
How do you know whether an alcohol will react via Sn1 or Sn2?
Same rule as for haloalkanes
How can alcohols be prepared?
Alkyl Halide Hydrolysis Acid catalysed addition of H2O Hydroboration-oxidation Reduction of aldehyde/ketone/ester Grignard reagents with Methanal, other aldehydes, ketone, esters or acyl chlorides.
What is the mechanism of an alcohol being formed via alkyl halide hydrolysis?
CH3Br + OH- –> CH3OH + Br- (Sn2)
(CH3)3CCl +H2O –> (CH3)3C+ +Cl –H2O–> (CH3)3CO+H2 — -H –> (CH3)3COH + HCl
What is the mechanism of an alcohol being formed via acid catalysed addition of H2O?
CH3CH=CH2 + H2O —(H+) –> CH3CH(OH)CH3 + CH3CH2CH2OH
What reagent do you use if you want the minor product of an addition reaction with alcohol?
B2H6/OH-
What is the mechanism of an alcohol being formed via hydroboration oxidation?
CH3CH=CH2 —(B2H6/H+)–> CH3CH2CH2BrH2 —> CH3CH2CH2OH
What does an aldehyde reduce to?
Primary aclohol
What does a ketone reduce to?
Secondary alcohol
What does an ester reduce to?
2x primary aclohols
What are the reagents you could use to reduce an aldehyde/ketone/ester?
LiAlH4 or NaBH4 with H3O+
What is formed when methanal reacts with a grignard reagent?
Primary alcohol with an extra carbon
What is formed when an aldehyde other than methanal reacts with a grignard reagent?
Secondary aclohol
What is formed when a ketone reacts with a grignard reagent?
Tertiary alcohol
What is formed when an ester or acid chloride reacts with a grignard reactant?
A tertiary alcohol is formed with 2 identical R groups.
What are the ways in which new C bonds can be formed?
Grignard reagents, nitriles, and alkynides (Grignard most likely)
What are the reactions an alcohol can perform?
Substitution
Elimination
Oxidation
What reagents are needed for an alcohol to form a haloalkane?
Addition of SOCl2 (if primary or secondary) or HCl (if tertiary)
What is the mechanism of Sn1 and Sn2 alcohol substitution?
CH3OH –(SOCl2) –> CH3Cl
(CH3)3COH + HCl –> (CH3)3CCl + H2O
What reagents are needed for an alkoxide to form an ether?
CH3CH2O- + RX –> CH3CH2COR + X-
What reagent is needed to form an alkene from an alcohol?
Concentrated H2SO4 and Heat.
Why does the alcohol have to be protonated (unlike the haloalkane) to form an alkene?
Because OH on its own is a poor leaving group, but H2O is very good.
What is the mechanism of a tertiary alcohol becoming an alkene?
CH3CH2OH —>H3O+/Heat—> CH3CH2OH2+ —> CH3 CH2+ +H2O —-> CH2=CH2
What is the mechanism of a 1/2 alcohol becoming an alkene?
CH3CH2OH + H2O—> transition state with a bond breaking between H anc C and C and OH2+, with a bond forming between H and OH and C and C
What do primary alcohols form when they are oxidised with H2CrO4?
Carboxylic acids
What to primary alcohols form when they are oxidised with PCC?
Aldehydes
What do secondary alcohols form when they are oxidised with H2CrO4?
Ketones
How are ketones formed on a ring structure?
Acid chloride + AlCl3 —> Ph-COCH3 + HCl
How do A/K undergo nucleophilic addition? (general)
RCOR + Nu- —> RC(O-)NuR — (H+) —> RC(OH)NuR (Only works with strong nucleophile)
What is a second way for A/K to undergo nucleophilic substitution?
RCOR + H+ —> RCOHR +Nu-H —-> RC(OH)Nu-H)R — (-H+) –> RC(OH)NuR
What does the oxonium ion method of a/k substitution require?
A weak nucleophile with an Nu-H bond.
How does the rate of reaction for a/k nucleophilic substitution change depending on the carbonyl’s R groups?
2Hs = fast
1H 1Alkyl/aryl = between
2alkyl/aryl = slow
Why does the trend in reaction rate for a/k substitution exist?
This is due to the electronic and steric effect changing the size of the delta +/- charges.
What is the reagent needed for an a/k to react with cyanide?
-CN/H3O+
What is the mechanism for an a/k reaction with -CN?
RCOR + -CN –> RCO(-)CNR –> RC(OH)CNR —-(H3O+) RC(OH)COOHR
What are possible oxygen nucleophiles that can be added to an a/k?
H2O, ROH
What is the reaction of an a/k reacting with water?
RCOR + H2O –> RC(OH2)R
What should be remembered about an a/k reaction with water?
Alkehydes favor the products more than ketones due to H2O being a good leaving group
What is the mechanism of an a/k reaction with an alcohol?
- RCOR + H+ —>RCOHR + ROH –> RC(OH)(OHR+)R — (-H) RC(OH)(OR)R (Called a hemiacetal)
- RC(OH)(OR)R + ROH —> RC(OR)2R +H2O (called an acetal)
Why are acetals important?
They serve as ‘protecting groups’ in the synthesis of some molecules
What are some nitrogen nucleophiles which a/ks could react with?
RNH2
NH2OH
H2NNH2
What is the mechanism for an a/k reaction with a nitrogen nucleophile?
RCOR + R’NH2 RC(OH)(NH2R’+)R —(-H2O)–> R(C=NR’)R
What is RC(NR)R called?
An imine
What is RC(NOH)R called?
An oxime
What is RC(NH2)R called?
A hydrazone
How do you remember what reagent to use when forming a compound using a nitrogen reagent?
It’s always (whatever you want) attached to an NH2 group.
What is an alpha carbon?
A carbonyl carbon
What is the requirement for a carbonyl to form an enol or enolate?
It must have an H on a vicinal C to the alpha carbon
How does a carbonyl carbon form an enol?
CH-C=O + HB —> (Sn2 transition state) C=COH + HB
How does a carbonyl carbon form an enolate?
CH-C=O + B- —> C=CO- + HB
Which is more useful out of an enol and enolate?
Enolate as it’s negatively charged and so way more reactive and useful for synthesis.
How is the enolate anion stabilised?
It can delocalise its charge to the vicinal Carbon
Why is an enol difficult to isolate?
It exists almost entirely in its ketone form (more stable)
Why do enols spend almost all their time in keto form?
The C=O bond is stronger than the C=C bond, making it more stable
What does tautomerisation mean for the isolation of an enolate anion?
A strong base is needed (OH-, RO-, NH2- or H-)
What can enols and enolates be used for?
Alkylation reactions- joining of an R group.
How does alkylation proceed when acid catalysed?
An RX + the enol causes the R to join to the double bond, and the O double bond to reform. This causes the R group to join the alpha carbon and a carbonyl carbon, with expulsion of HX.
How does alkylation proceed when base catalysed?
An RX + an enolate cause the R to join the double bond, and the O double bond to reform. This causes the R to join the alpha carbon and a carbonyl carbon, with expulsion of X-.
Which is better and why- acid or base catalysed alkylation?
Base catalysed as the enolate is more reactive than the enol.
How does an aldol form?
A base removes the alpha hydrogen from a carbonyl compound, forming a carbanion. Following this, a second carbonyl reacts with the anion, and the negative carbanion carbon joins to the delta positive carbonyl carbon, forming a bigger structure. The negatively charged ex-carbonyl Oxygen then re-takes the hydrogen, forming an alcohol on one side joined to an aldehyde on the other- an aldol.
How does an aldol form an enal?
If the alcohol group neighbours a Carbon with a Hydrogen, these can react to come off, forming a double bond in their place- giving the final product as an enal.
What needs to be remembered about substituents on Carboxylic acids?
With substituents joined directly to acids in straight chained molecules, or ortho/para in aromatic acids, the acid’s pKa is affected by whether the substituent is withdrawing or donating. If the directly attached atom of the substituent has a delta + charge it withdraws electrons, and those with lone pairs of electrons donate electrons.
Do electron donating groups increase or decrease acid strength?
They decrease the acid strength as larger alkyl groups push more electrons into an already negatively charged compound, destabilizing the ion and making it less likely to form.
Do electron withdrawing groups increase or decrease acid strength?
They increase acid strength as they have a slight delta plus charge, allowing them to absorb the negative charge and make a more stable resonance structure, making the ion more likely to form.
Do halogens on the alkyl substituent increase or decrease the acid strength?
Increase as they are highly electronegative, making the attached C even more positive and able to accept an electron.
Are acids or phenols more soluble in Hydrogencarbonate (acid) and why?
Acids are more soluble as the conjugate acid which is formed is weaker than the acid itself, so is more product favored. However, the phenol is a weaker acid than the potential conjugate, and so is not as soluble as the reaction is reactant favored.
What are the ways of preparing a carboxylic acid?
Oxidation of a primary alcohol/aldehyde
From a grignard reagent with CO2
From a nirile
How do you prepare a carboxylic acid from a grignard reagent and CO2?
R-MgX + CO2 —> R-C=O(OMgX) –(H3O+)–> RCOOH
How do you make carboxylic acid from a nitrile?
R-X + -CN –> RCN + Br- –(H3O+)–> RCOOH + NH3
What are the derivatives of carboxylic acids?
Acid chlorides, Carboxylic acids, Acid Anhydrides, Esters and Amides
What is the process of substituting a carboxylic acid derivative?
RCOY + Nu- –> RC(Nu)(O-)Y –> RCONu + Y-
What is the reactivity order of carboxylic acid derivatives?
Acid Chlorides > Acid Anhydrides > Esters > Amides
What step is the slow step of the substitution of carboxylic acid derivatives?
The joining of the nucleophile
Why is the reactivity order the way it is?
As the breaking of the C-Y bond is the slow step, the reactivity has nothing to do with the leaving ability of Y. If the Y group is electron withdrawing, the C will be more positive, allowing it to be attacked more effectively by the nucleophile. However, if the group is electron donating it makes the C less positive, making it less reactive with a nucleophile.
How do you prepare an acid chloride?
RCOOH + SOCl2 –> RCOCl + HCl + H2O
What can acid chlorides form?
Acids (H2O), Amides (NH2R), Esters (ROH) and Anhydrides (RCOOH)
How do acid chlorides react with grignard reagents?
RCOCl —(2R’MGX/H3O+)—>RC(R’)2OH
What is an acid anhydride?
R-C=OOC=O-R
How is an acid anhydride formed?
- 2x Carboxylic acids with P2O5 form acid anhydride symmetrically with H2O
- Acid chloride with a carboxylate ion to form unsymmetrical acid anhydride and Hydrogen Chloride
How can acid anhydrides react?
Form an ester with an alcohol, amide with NH2R and a carboxylic acid with H2O
How is an ester formed?
Acid chloride + alcohol/phenol
Carboxylic acid + Alcohol
Acid anhydride + alcohol
How do esters react?
They are slower than acid chlorides or anhydrides.
They form amides with RNH2 and carboxylic acids with H2O in either acidic or basic conditions (to form a carboxylic acid and alcohol)
They can also be reduced to produce two primary alcohols, (the carbonyl side is always primary)
Finally, grignard reagents form a tertiary alcohol with two equivalent groups (using two equivalents of ester).
What biological application do esters have?
Polyesters are used to form stitches, which are broken down by the slight acidity of body fluids- thus forming dissolvable stitches.
How do you make amides?
From an acid anhydride, ester or acid chloride with RNH2
How do amides react?
They form RNH3+ and a carboxylate anion with H3O+ and heat, and further reaction of the RNH3+ with OH- forms RNH2
With H2O to form Acids
How do polypeptides form?
diacid chlorides and diamides form a peptide bond
Why are amides neutral, rather than basic?
The resonance from the double bond on O to the N reduces the availability of the electron pairs.
What are the seven types of reactions?
Electrophilic Addition Nucleophilic Addition Nucleophilic Substitution Nucleophilic Acyl Substitution Elimination Oxidation Electrophilic Aromatic Substitution
What are the three combinations of reactions?
Nucleophilic Addition with Nucleophilic Substitution
Nucleophilic Addition with Elimination
Nucleophilic Acyl Substitution with Nucleophilic Addition
What are some examples of electrophilic addition?
Alkene + H2/Pd OR X2 OR HX OR H2O/H2SO4
Alkyne + Lindlar Catalyst OR Li/NH3/H3O+ OR H2/Pd OR X2 OR HX OR H2O/H2SO4
What are some examples of Nucleophilic addition?
C=O + NaBH4/H3O+ OR ROH/H+ OR CN-/H3O+ OR RMgX/H3O+
What are some examples of Nucleophilic substitution?
COH + HCl
CX + OH- OR CN- OR C=_CR- OR OR-
What are some examples of Nucleophilic Acyl substitution?
C=OR + SOCl2 OR NH2R OR RCOOH OR ROH
What are some examples of elimination?
CHCX + OH-
CHCOH + H2SO4 conc
CXHCXH + OH-
What are some examples of Oxidation?
Alcohol –> Ketone/aldehyde/carb. acid
What are some examples of Nucleophilic addition + substitution?
Aldehyde/ketone to hemiacetal & acetal using (2)ROH/H+
What are some examples of nucleophilic addition + elimination?
Aldehyde/ketone to imine, hydrazone and oxine
What are some examples of Nucleophilic acyl substitution with nucleophilic addition?
Ester with LiAlH4 and H3O+ to form primary alcohols
Ester/Acid chloride with 2RMgX?H3O+ to form a tertiary alcohol with two identical R groups
How are amines classed?
Primary, secondary or tertiary based on how many Cs there are bonded to the N
What are aromatic amines?
NR2 groups bonded directly to the benzene ring
Why are amines good nucleophiles or bases?
They have a lone pair of electrons on the N, and so are able to accept a proton
What can be used to determine the basicity of an amine?
The higher the pKa (weaker acid) the conjugate acid is, the stronger the basicity of the amine
What determines which class of amine is more basic and why? What is the trend?
Generally, the more R substituents on an amine, the more basic it is as the extra electron density on the N makes it more negative. However, a tertiary amine doesn’t follow this pattern as the increased R groups make the compound more crowded, preventing it from gaining a proton as efficiently.
Why are aromatic amines much weaker than alkylamines?
The lone pair of electrons on N is donated into the ring, causing it to become resonance stabilized and less likely to react
What effect do electron withdrawing and donating groups have on an arylamine’s basicity?
Electron withdrawing groups decrease basicity as they further stabilize the lone pair of electrons, making them less able to react as a base
Electron donating groups increase basicity as they add to the already negative charge, making it more concentrated and allowing N to act as a base
How are alkylamines prepared, but what is the issue with this?
They are prepared by substituting haloalkanes with NHR2 groups. However, each product is more reactive than the reactants, so you get a the produced CH3CH2NH2 reacing with the CH3CH2Br used to produce it. This results in a secondary amine, then tertiary, and eventually a quarternary ammonium salt. It is therefore not a good way of isolating amines, as a mixture results
How do arylamines form by subtitution?
By reacting Ph-NO2 with Fe/H+ and OH-, and NH2 group is substituted onto the ring, or an NHR or NR2 groups, if a 2ry or 3ry amine is requried.
How do amines form from reduction?
Reduction of a nitrile, primary amide, primary imine or oxime with LiAlH4/H3O+ results in a primary amine
Reduction of a secondary amide or an N-substituted imine results in a secondary alcohol
Reduction of a tertiary amide results in a tertiary bond
NB: The C with the original multiple bond always becomes a CH2 group!
How do amines react with halogens/acyl chlorides?
The reactions with haloalkanes are unstable, as mentioned in another card
Primary amines reacting with acyl chlorides form a secondary amide, while secondary amines form tertiary amides.
Tertiary amines cannot react with acid chlorides as they don’t have a removable H.
How do primary arylamines react?
They form diazonium ions in the presence of HNO2 at 0 degrees celsius
Why are diazonium ions important?
They are intermediates in promoting the formation of meta substituted products, as they are meta directors which can be substituted after direction to form an o/p director. This allows the formation of a benzene ring with two o/p directors meta to one another
